• cholesterol
• colocalization
• ER
• I1061T
• lysosomes
• mitochondria
• Niemann Pick type C
• NPC1

Over 200 disease-causing mutations have been identified in the NPC1 gene. NPC1 is a 1278 amino acid protein with 13 transmembrane domains that is crucial for normal cholesterol homeostasis. The most prevalent mutation, NPC1I1061T, is predicted to lie within the cysteine-rich luminal domain and is associated with the classic juvenile-onset phenotype of Niemann-Pick type C disease.
To gain some insights on how loss of NPC1 function leads to neurodegeneration we have examined the global pattern of expression the protein in HN9.10e a neuronal cell line. In this research we studied first the distribution of the protein in the cell and motility and then we focused on the cell suborganelles seeking evidence for mislocalization of the protein as well as structural damage.
Our research shows that the NPC1I1061T protein fails to advance in the secretory pathway and remains trapped into the endoplasmic reticulum with consequent alteration in the reticulum structure and function. Further analyses reveal that the presence of missense mutation of NPC1 protein affects also mitochondria functions.
Understanding the behaviour and properties of organelles containing NPC1 will help to address the substantial mysteries of NPC1 function. This work could be useful to understand the basis of Niemann-Pick disease and devise prevention or treatment strategies.